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Differential effects of cholesterol and its immediate biosynthetic precursors on membrane organization

机译：胆固醇及其直接生物合成前体对膜组织的差异作用

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摘要

Cholesterol is the most representative sterol present in vertebrate membranes and is the end product of the long and multistep sterol biosynthetic pathway. 7-Dehydrocholesterol- (7-DHC) and desmosterol are the immediate biosynthetic precursors of cholesterol in the Kandutsch-Russell and Bloch pathway. In this article, we have monitored the effect of cholesterol and its two immediate biosynthetic precursors on biophysical and dynamic properties of fluid and gel phase membranes. Toward this goal, we have used fluorescent membrane probes, DPH and TMA-DPH, and the hydrophobic probe, pyrene. Our results using these probes show that although both 7-DHC and desmosterol differ with cholesterol in one double bond, they exhibit differential effects on membrane organization and dynamics. Importantly, we show that the effect of cholesterol and desmosterol on membrane organization and dynamics is similar in most cases, while 7-DHC has a considerably different effect. This demonstrates that the position of the double bond in sterols is an important determinant in maintaining membrane order and dynamics. These results assume relevance since the accumulation of cholesterol precursors have been reported to result in severe pathological conditions.
机译：胆固醇是存在于脊椎动物膜中的最具代表性的甾醇，是漫长而多步的甾醇生物合成途径的终产物。 7-脱氢胆固醇-（7-DHC）和去氢甾醇是坎杜奇-罗素和布洛赫途径中胆固醇的直接生物合成前体。在本文中，我们已经监测了胆固醇及其两种直接生物合成前体对流体和凝胶相膜的生物物理和动态特性的影响。为了实现这一目标，我们使用了荧光膜探针DPH和TMA-DPH，以及疏水探针pyr。使用这些探针的结果表明，尽管7-DHC和去氢甾醇在一个双键中与胆固醇不同，但它们对膜的组织和动力学表现出不同的影响。重要的是，我们表明，在大多数情况下，胆固醇和去甾醇对膜组织和动力学的影响相似，而7-DHC的影响却大不相同。这证明了固醇中双键的位置是维持膜秩序和动力学的重要决定因素。这些结果具有相关性，因为据报道胆固醇前体的积累会导致严重的病理状况。

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